General Reagent Free Route to pH Responsive Polyacryloyl Hydrazide Capped Metal Nanogels for Synergistic Anticancer Therapeutics

Abstract

Herewith, we report a facile synthesis of pH responsive polyacryloyl hydrazide (PAH) capped silver (Ag) or gold (Au) nanogels for anticancer therapeutic applications. A cost-effective instant synthesis of PAH-Ag or PAH-Au nanoparticles (NPs) possessing controllable particle diameter and narrow size distribution was accomplished by adding AgNO3 or AuCl to the aqueous solution of PAH under ambient conditions without using any additional reagent. PAH possessing carbonyl hydrazide pendant functionality served as both reducing and capping agent to produce and stabilize the NPs. The stability analysis by UV-vis, dynamic light scattering, and transmission electron microscopy techniques suggested that these NPs may be stored in a refrigerator for at least up to 2 weeks with negligible change in conformation. The average hydrodynamic size of PAH-Ag NPs synthesized using 0.2 mmol/L AgNO3 changed from 122 to 226 nm on changing the pH of the medium from 5.4 to 7.4, which is a characteristic property of pH responsive nanogel. Camptothecin (CPT) with adequate loading efficiency (6.3%) was encapsulated in the PAH-Ag nanogels. Under pH 5.4 conditions, these nanogels released 78% of the originally loaded CPT over a period of 70 h. The antiproliferative potential of PAH-Ag-CPT nanogels (at [CPT]=0.6 μg/mL) against MCF-7 breast adeno-carcinoma cells were ∼350% higher compared to that of the free CPT as evidenced by high cellular internalization of these nanogels. Induction of apoptosis in MCF-7 breast adeno-carcinoma cells by PAH-Ag-CPT nanogels was evidenced by accumulation of late apoptotic cell population. Drug along with the PAH-Ag NPs were also encapsulated in a pH responsive hydrogel through in situ gelation at room temperature using acrylic acid as the cross-linker. The resulting hydrogel released quantitative amounts of both drug and PAH-Ag NPs over a period of 16 h. The simplicity of synthesis and ease of drug loading with efficient release render these NPs a viable candidate for various biomedical applications, and moreover this synthetic procedure may be extended to other metal NPs.

Tunable metal-enhanced fluorescence by pH-responsive polyacryloyl hydrazide capped Ag nanoparticles

“…In addition, the presence of PAH on the surface of the Ag NPs can resist the oxidation of Ag 0 to Ag + and reduce the toxicity associated with Ag NPs. 26 We also conrmed the above-mentioned results through the experimental phenomena. When the solution of AgNO 3 was added into the PAH aqueous solution at ambient temperature, a characteristic yellow color of the reaction mixture appeared within 15 min, suggesting the formation of NPs.…”

“…PAH-Ag NPs were prepared without a reducing agent or modi-er. 26 Briey, 250 mL of AgNO 3 aqueous solution (0.05 mol L À1 ) was added to 25 mL of PAH aqueous solution (2% (w/v)), then the mixture was stirred for 30 min at room temperature. The resulting reddish brown solution was puried by dialysis against deionized water for 24 h, collected by centrifugation, and then dispersed in deionized water.…”

“…24,25 Owing to abundant hydrazide functionality, PAH can not only serve as the reducing agent for the metal ion precursors, but can also swily encapsulate the surface and stabilize the metal NPs. 26 PAH was used as a nanoreactor to synthesize Ag NPs and at the same time Ag NPs were dispersed in the stimuli nanoparticles. Therefore, we employed tunable MEF effects by adjusting the interaction distance between the uorophores and the Ag NPs owing to the pH responsive swollen-shrunken state of PAH under pH stimuli.…”

Exploring Factors for the Design of Nanoparticles as Drug Delivery Vectors

“…Many articles have focused on the drug delivery applications of organic‐based NPs, like liposomes, dendrimers, cyclodextrins,, gelatin‐based, polymeric, protein, hybrid and others …”

A New Smart Surface-Enhanced Raman Scattering Sensor Based on pH-Responsive Polyacryloyl Hydrazine Capped Ag Nanoparticles

“…Polyacryloyl hydrazide (PAH) is a pH-responsive polymer, which has been applied to various biomedical fields [ 16 ]. Owing to abundant hydrazide functional groups on PAH, PAH can serve as not only the end-capping reagent but also the reducing agent of the metal ion precursors to easily prepare Ag nanoparticles (NPs) [ 17 ]. The swelling-shrinking behavior of responsive PAH can control the distance between Ag NPs and the target molecules under external pH stimuli, resulting in the tunable LSPR and further controlled SERS.…”